Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDRVYLADYGLSYRYCPNG 79
Cdd:cd14123   106 MVMDRLGTDLQKILIDNGGqFKKTTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYRNPNEVYLADYGLSYRYCPNG 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEAKLDDPVAVQTAKTNLLDELPESVLK 159
Cdd:cd14123   186 NHKEYKENPRKGHNGTIEFTSLDAHKGVAPSRRGDLEILGYCMLHWLCGKLPWEQNLKNPVAVQEAKAKLLSNLPDSVLK 265

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1720367387 160 WAPSGSSCSELVKYLMYVHNLAYDDKPDYQKLKKILN 196
Cdd:cd14123   266 WSTGGSSSMEIAQFLSRVKDLAYDEKPDYQALKKILS 302

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins. VRK2 exists as two alternative splice forms, A and B, which differ in their C-terminal regions. VRK2A, the predominant isoform, contains a hydrophobic tail and is anchored to the ER and mitochondria. It is expressed in all cell types. VRK2B lacks a membrane-anchor tail and is detected in the cytosol and the nucleus. Like VRK1, it can stabilize p53. VRK2B functionally replaces VRK1 in the nucleus of cell types where VRK1 is absent. VRK2 modulates hypoxia-induced stress responses by interacting with TAK1, an atypical MAPK kinase kinase which triggers cascades that activate JNK following oxidative stress. VRK2 also interacts with JIP1, a scaffold protein that assembles three consecutive members of a MAPK pathway. This interaction prevents the association of JNK with the signaling complex, leading to reduced phosphorylation and AP1-dependent transcription. The VRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDRVYLADYGLSYRYCPNG 79
Cdd:cd14123   106 MVMDRLGTDLQKILIDNGGqFKKTTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYRNPNEVYLADYGLSYRYCPNG 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEAKLDDPVAVQTAKTNLLDELPESVLK 159
Cdd:cd14123   186 NHKEYKENPRKGHNGTIEFTSLDAHKGVAPSRRGDLEILGYCMLHWLCGKLPWEQNLKNPVAVQEAKAKLLSNLPDSVLK 265

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1720367387 160 WAPSGSSCSELVKYLMYVHNLAYDDKPDYQKLKKILN 196
Cdd:cd14123   266 WSTGGSSSMEIAQFLSRVKDLAYDEKPDYQALKKILS 302

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERL-GIDLQKLLDQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNpdRVYLADYGLSYRYcpnG 79
Cdd:COG0515    84 LVMEYVeGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDG--RVKLIDFGIARAL---G 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKghnGTIEFTSLDAHKGVAPSRRSDVEILGyCMLHWLF-GKLPWEAklDDPVAVQTAktnLLDELPESVL 158
Cdd:COG0515   159 GATLTQTGTVV---GTPGYMAPEQARGEPVDPRSDVYSLG-VTLYELLtGRPPFDG--DSPAELLRA---HLREPPPPPS 229

                  ....
gi 1720367387 159 KWAP 162
Cdd:COG0515   230 ELRP 233

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720367387   1 MVME--RLGiDLQKLLDQNGGfkKLTVLQLgIRM-LDV---LEYIHENEYVHGDIKAANLLLDftNPDRVYLADYGLS 72
Cdd:pfam07714  78 IVTEymPGG-DLLDFLRKHKR--KLTLKDL-LSMaLQIakgMEYLESKNFVHRDLAARNCLVS--ENLVVKISDFGLS 149

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720367387   1 MVMERL-GIDLQKLLDQNG-GFKKLTVLQLGIrmldvleyIHENEYVHGDIKAANLLLdftNPDRVYLADYGLSYR 74
Cdd:TIGR03724  74 IVMEYIeGKPLKDVIEENGdELAREIGRLVGK--------LHKAGIVHGDLTTSNIIV---RDDKVYLIDFGLGKY 138

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins. VRK2 exists as two alternative splice forms, A and B, which differ in their C-terminal regions. VRK2A, the predominant isoform, contains a hydrophobic tail and is anchored to the ER and mitochondria. It is expressed in all cell types. VRK2B lacks a membrane-anchor tail and is detected in the cytosol and the nucleus. Like VRK1, it can stabilize p53. VRK2B functionally replaces VRK1 in the nucleus of cell types where VRK1 is absent. VRK2 modulates hypoxia-induced stress responses by interacting with TAK1, an atypical MAPK kinase kinase which triggers cascades that activate JNK following oxidative stress. VRK2 also interacts with JIP1, a scaffold protein that assembles three consecutive members of a MAPK pathway. This interaction prevents the association of JNK with the signaling complex, leading to reduced phosphorylation and AP1-dependent transcription. The VRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDRVYLADYGLSYRYCPNG 79
Cdd:cd14123   106 MVMDRLGTDLQKILIDNGGqFKKTTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYRNPNEVYLADYGLSYRYCPNG 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEAKLDDPVAVQTAKTNLLDELPESVLK 159
Cdd:cd14123   186 NHKEYKENPRKGHNGTIEFTSLDAHKGVAPSRRGDLEILGYCMLHWLCGKLPWEQNLKNPVAVQEAKAKLLSNLPDSVLK 265

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1720367387 160 WAPSGSSCSELVKYLMYVHNLAYDDKPDYQKLKKILN 196
Cdd:cd14123   266 WSTGGSSSMEIAQFLSRVKDLAYDEKPDYQALKKILS 302

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDRVYLADYGLSYRYCPNG 79
Cdd:cd14122   104 MIMDRFGSDLQKIYEANAKrFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSYKNPDQVYLVDYGLAYRYCPEG 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEAKLDDPVAVQTAKTNLLDELPESVLK 159
Cdd:cd14122   184 VHKEYKEDPKRCHDGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHLPWEDNLKDPNYVRDSKIRYRDNISELMEK 263

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1720367387 160 WAPSGSSCSELVKYLMYVHNLAYDDKPDYQKLKKIL 195
Cdd:cd14122   264 CFPGKNKPGEIRKYMETVKLLGYTEKPLYPHLREIL 299

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDF-TNPDRVYLADYGLSYRYCPN 78
Cdd:cd14016    73 MVMDLLGPSLEDLFNKCGRkFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMGLgKNSNKVYLIDFGLAKKYRDP 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  79 GNHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPW----------------EAKLDDPVAV 142
Cdd:cd14016   153 RTGKHIPYREGKSLTGTARYASINAHLGIEQSRRDDLESLGYVLIYFLKGSLPWqglkaqskkekyekigEKKMNTSPEE 232

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720367387 143 qtaktnLLDELPEsvlkwapsgsscsELVKYLMYVHNLAYDDKPDYQKLKKIL 195
Cdd:cd14016   233 ------LCKGLPK-------------EFAKYLEYVRSLKFEEEPDYDYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 delta and epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. The delta and epsilon isoforms of CK1 play important roles in circadian rhythm and cell growth. They phosphorylate PERIOD proteins (PER1-3), which are circadian clock proteins that fulfill negative regulatory functions. PER phosphorylation leads to its degradation. However, CRY proteins form a complex with PER and CK1delta/epsilon that protects PER from degradation and leads to nuclear accummulation of the complex, which inhibits BMAL1-CLOCK dependent transcription activation. CK1delta/epsilon also phosphorylate the tumor suppressor p53 and the cellular oncogene Mdm2, which are key regulators of cell growth, genome integrity, and the development of cancer. This subfamily also includes the CK1 fungal proteins Saccharomyces cerevisiae HRR25 and Schizosaccharomyces pombe HHP1. These fungal proteins are involved in DNA repair. The CK1 delta/epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQ-NGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDF-TNPDRVYLADYGLS--YRYC 76
Cdd:cd14125    73 MVMDLLGPSLEDLFNFcSRKFSLKTVLMLADQMISRIEYVHSKNFIHRDIKPDNFLMGLgKKGNLVYIIDFGLAkkYRDP 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  77 PNGNHKQYQEDprKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPW----------------EAKLDDPV 140
Cdd:cd14125   153 RTHQHIPYREN--KNLTGTARYASINTHLGIEQSRRDDLESLGYVLMYFNRGSLPWqglkaatkkqkyekisEKKMSTPI 230

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720367387 141 avqtaktnlldelpESVLKWAPsgsscSELVKYLMYVHNLAYDDKPDYQKLKKIL 195
Cdd:cd14125   231 --------------EVLCKGFP-----SEFATYLNYCRSLRFDDKPDYSYLRRLF 266

Catalytic domain of the Serine/Threonine protein kinase, Fungal Casein Kinase 1 homolog 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. This subfamily is composed of fungal CK1 homolog 1 proteins, also called Yck1 in Saccharomyces cerevisiae and Cki1 in Schizosaccharomyces pombe. Yck1 (or Yck1p) and Cki1 are plasma membrane-anchored proteins. Yck1 phosphorylates and regulates Khd1p, a RNA-binding protein that represses translation of bud-localized mRNA. Cki1 phosphorylates and regulates phosphatidylinositol (PI)-(4)P-5-kinase, which catalyzes the last step in the sythesis of PI(4,5)P2, which is involved in actin cytoskeleton remodeling and membrane traffic. The fungal CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG-FKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLL---DFTNPDRVYLADYGLS--YR 74
Cdd:cd14127    73 LVIDLLGPSLEDLFDLCGRkFSVKTVVMVAKQMLTRVQTIHEKNLIYRDIKPDNFLIgrpGTKNANVIHVVDFGMAkqYR 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  75 YCPNGNHKQYQEdpRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEA------KLDDPVAVQTAKTN 148
Cdd:cd14127   153 DPKTKQHIPYRE--KKSLSGTARYMSINTHLGREQSRRDDLEALGHVFMYFLRGSLPWQGlkaatnKQKYEKIGEKKQST 230

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1720367387 149 LLDELPESVlkwaPsgsscSELVKYLMYVHNLAYDDKPDYQKLKKIL 195
Cdd:cd14127   231 PIRDLCEGF----P-----EEFAQYLEYVRNLGFDETPDYDYLRGLF 268

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQ-NGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDR---VYLADYGLSYRY- 75
Cdd:cd14126    73 MVLELLGPSLEDLFDLcDRTFSLKTVLMIAIQLISRIEYVHSKHLIYRDVKPENFLIGRQSTKKqhvIHIIDFGLAKEYi 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  76 -CPNGNHKQYQEdpRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEA-----------KLDDpVAVQ 143
Cdd:cd14126   153 dPETNKHIPYRE--HKSLTGTARYMSINTHLGKEQSRRDDLEALGHMFMYFLRGSLPWQGlkadtlkeryqKIGD-TKRA 229

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1720367387 144 TAKTNLLDELPEsvlkwapsgsscsELVKYLMYVHNLAYDDKPDYQKLKKI 194
Cdd:cd14126   230 TPIEVLCENFPE-------------EMATYLRYVRRLDFFETPDYDYLRKL 267

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERL-GIDLQKLLDQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNpdRVYLADYGLSYRYcpnG 79
Cdd:COG0515    84 LVMEYVeGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDG--RVKLIDFGIARAL---G 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  80 NHKQYQEDPRKghnGTIEFTSLDAHKGVAPSRRSDVEILGyCMLHWLF-GKLPWEAklDDPVAVQTAktnLLDELPESVL 158
Cdd:COG0515   159 GATLTQTGTVV---GTPGYMAPEQARGEPVDPRSDVYSLG-VTLYELLtGRPPFDG--DSPAELLRA---HLREPPPPPS 229

                  ....
gi 1720367387 159 KWAP 162
Cdd:COG0515   230 ELRP 233

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLL--DQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDF--TNPDRVYLADYGLSYRYC 76
Cdd:cd14129    73 VVMQLQGRNLADLRrsQSRGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKCYMLDFGLARQFT 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  77 pngNHKQYQEDPRK--GHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEaKLDDPVAVQTAKTNLLDELp 154
Cdd:cd14129   153 ---NSCGDVRPPRAvaGFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR-KIKDKEQVGSIKERYEHRL- 227

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1720367387 155 esVLKWAPsgsscSELVKYLMYVHNLAYDDKPDYQKLKKILN 196
Cdd:cd14129   228 --MLKHLP-----PEFSVFLDHISGLDYFTKPDYQLLVSVFD 262

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Genetic variations in TTBK1 are linked to Alzheimer's disease (AD). Hyperphosphorylated tau is a major component of paired helical filaments that accumulate in the brain of AD patients. Studies in transgenic mice show that TTBK1 is involved in the phosphorylation-dependent pathogenic aggregation of tau. The TTBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQN--GGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDF--TNPDRVYLADYGLSYRYC 76
Cdd:cd14130    73 VVMQLQGRNLADLRRSQprGTFTLSTTLRLGKQILESIEAIHSVGFLHRDIKPSNFAMGRlpSTYRKCYMLDFGLARQYT 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  77 pngNHKQYQEDPRK--GHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEaKLDDPVAVQTAKTNLLDELp 154
Cdd:cd14130   153 ---NTTGEVRPPRNvaGFRGTVRYASVNAHKNREMGRHDDLWSLFYMLVEFAVGQLPWR-KIKDKEQVGMIKEKYEHRM- 227

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1720367387 155 esVLKWAPsgsscSELVKYLMYVHNLAYDDKPDYQKLKKIL 195
Cdd:cd14130   228 --LLKHMP-----SEFHLFLDHIASLDYFTKPDYQLIMSVF 261

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  13 LLDQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNpDRVYLADYGLSYRYcpngNHKQYQEDPRKGH 92
Cdd:cd06630    93 LLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLVDSTG-QRLRIADFGAAARL----ASKGTGAGEFQGQ 167

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1720367387  93 N-GTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWEAK 135
Cdd:cd06630   168 LlGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAE 211

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGgfKKLTVLQLGIRM---LDVLEYIHENEYVHGDIKAANLLLDftNPDRVYLADYGLSYRYCP 77
Cdd:cd07840    81 MVFEYMDHDLTGLLDNPE--VKFTESQIKCYMkqlLEGLQYLHSNGILHRDIKGSNILIN--NDGVLKLADFGLARPYTK 156

                  ...
gi 1720367387  78 NGN 80
Cdd:cd07840   157 ENN 159

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720367387   1 MVMERLGIDLQKLLDQNG-GFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDFTNPDrVYLADYGLSYRY 75
Cdd:cd05118    78 LVFELMGMNLYELIKDYPrGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQ-LKLADFGLARSF 152

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGgfKKLTVLQLGIRMLDVLE---YIHENEYVHGDIKAANLLLDftNPDRVYLADYGLSYRYcp 77
Cdd:cd07866    92 MVTPYMDHDLSGLLENPS--VKLTESQIKCYMLQLLEginYLHENHILHRDIKAANILID--NQGILKIADFGLARPY-- 165

                          90       100
                  ....*....|....*....|....
gi 1720367387  78 NGNHKQYqedPRKGHNGTIEFTSL 101
Cdd:cd07866   166 DGPPPNP---KGGGGGGTRKYTNL 186

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   2 VMERLG-IDLQKLLDqnGGFKKLTvlqLGIRM---LDV---LEYIHENEYVHGDIKAANLLLDftNPDRVYLADYGLSYR 74
Cdd:cd13979    80 IMEYCGnGTLQQLIY--EGSEPLP---LAHRIlisLDIaraLRFCHSHGIVHLDVKPANILIS--EQGVCKLCDFGCSVK 152

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  75 -YCPNGnhkqyQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWE 133
Cdd:cd13979   153 lGEGNE-----VGTPRSHIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYA 207

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMERLGIDLQKLLDQNGG------FKKLTVLQlgirMLDVLEYIHENEYVHGDIKAANLLLdftNPDRVYLADYGLSyr 74
Cdd:cd14131    79 MVMECGEIDLATILKKKRPkpidpnFIRYYWKQ----MLEAVHTIHEEGIVHSDLKPANFLL---VKGRLKLIDFGIA-- 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387  75 ycpngnhKQYQEDP----RKGHNGTIEFTS------LDAHKGVAP----SRRSDVEILG---YCMLHwlfGKLPWeAKLD 137
Cdd:cd14131   150 -------KAIQNDTtsivRDSQVGTLNYMSpeaikdTSASGEGKPkskiGRPSDVWSLGcilYQMVY---GKTPF-QHIT 218

                         170
                  ....*....|.
gi 1720367387 138 DPVAVQTAKTN 148
Cdd:cd14131   219 NPIAKLQAIID 229

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   1 MVMER-LGIDLQKLLDQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDftNPDRVYLADYGLSYR----- 74
Cdd:cd14010    71 LVVEYcTGGDLETLLRQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLD--GNGTLKLSDFGLARRegeil 148

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720367387  75 ----YCPNGNHKQYQEDPRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGyCMLHWLF-GKLPWEA 134
Cdd:cd14010   149 kelfGQFSDEGNVNKVSKKQAKRGTPYYMAPELFQGGVHSFASDLWALG-CVLYEMFtGKPPFVA 212

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720367387   7 GIDLQKLLDQNGGFKKLTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLDftNPDRVYLADYGLSYRYCPN----GNHK 82
Cdd:cd06628    90 GGSVATLLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVD--NKGGIKISDFGISKKLEANslstKNNG 167

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720367387  83 QyqedpRKGHNGTIEFTSLDAHKGVAPSRRSDVEILGYCMLHWLFGKLPWeAKLDDPVAVQTAKTNLLDELPE 155
Cdd:cd06628   168 A-----RPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPF-PDCTQMQAIFKIGENASPTIPS 234

tRNA A-37 threonylcarbamoyl transferase component Bud32 [Translation, ribosomal structure and biogenesis]; tRNA A-37 threonylcarbamoyl transferase component Bud32 is part of the Pathway/BioSystem: tRNA modification

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720367387   1 MVMERL-GIDLQKLLDQNGGFKKLtVLQLGirmlDVLEYIHENEYVHGDIKAANLLLDftnPDRVYLADYGLSYRYCP 77
Cdd:COG3642    33 LVMEYIeGETLADLLEEGELPPEL-LRELG----RLLARLHRAGIVHGDLTTSNILVD---DGGVYLIDFGLARYSDP 102